Skip to main content
SpringerLink
Log in

Biomarkers of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease

  • Original Article
  • Published:
World Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Background

Currently, there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease.

Methods

A total of 300 patients with Kawasaki disease were studied retrospectively. Laboratory data were compared between the intravenous immunoglobulin resistant (29 patients) and responsive groups, and between the groups with coronary artery lesions (48 patients) and without coronary artery lesions.

Results

The intravenous immunoglobulin resistant group had significantly higher D-dimer, globulin, interleukin-6 and serum ferritin levels in comparison to the intravenous immunoglobulin responder group. D-dimer level had a sensitivity of 87.0% and a specificity of 56.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 1.09 mg/L. Globulin had a sensitivity of 62.1% and a specificity of 82.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 34.7 g/L. Serum ferritin level had a sensitivity of 42.9% and a specificity of 88.8% for predicting intravenous immunoglobulin resistance at a cutoff point of 269.7 ng/mL. The patients with coronary artery lesions had higher D-dimer and tumor necrosis factor-α level. D-dimer level had a sensitivity of 50% and a specificity of 78.6% for predicting coronary artery lesions at a cutoff point of 1.84 mg/L. Based on analysis by multivariate logistic regression, serum ferritin and globulin were independent risks for intravenous immunoglobulin resistance, D-dimer was independent risk for coronary artery lesions.

Conclusions

Elevated serum ferritin, globulin and D-dimer levels are significantly associated with intravenous immunoglobulin resistance in Kawasaki disease. Moreover, serum D-dimer is significantly increased in Kawasaki disease with coronary artery lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135:e927–99.

    Article  PubMed  Google Scholar 

  2. Egami K, Muta H, Ishii M, Suda K, Sugahara Y, Iemura M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr. 2006;149:237–40.

    Article  CAS  PubMed  Google Scholar 

  3. Kobayashi T, Inoue Y, Takeuchi K, Okada Y, Tamura K, Tomomasa T, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113:2606–12.

    Article  Google Scholar 

  4. Mori M, Imagawa T, Yasui K, Kanaya A, Yokota S. Predictors of coronary artery lesions after intravenous gamma-globulin treatment in Kawasaki disease. J Pediatr. 2000;137:177–80.

    Article  CAS  PubMed  Google Scholar 

  5. Beiser AS, Takahashi M, Baker AL, Sundel RP, Newburger JW. A predictive instrument for coronary artery aneurysms in Kawasaki disease. US Multicenter Kawasaki Disease Study Group. Am J Cardiol. 1998;81:1116–1120.

  6. Honkanen VE, McCrindle BW, Laxer RM, Feldman BM, Schneider R, Silverman ED. Clinical relevance of the risk factors for coronary artery inflammation in Kawasaki disease. Pediatr Cardiol. 2003;24:122–6.

    Article  CAS  PubMed  Google Scholar 

  7. Sabharwal T, Manlhiot C, Benseler SM, Tyrrell PN, Chahal N, Yeung RS, et al. Comparison of factors associated with coronary artery dilation only versus coronary artery aneurysms in patients with Kawasaki disease. Am J Cardiol. 2009;104:1743–7.

    Article  PubMed  Google Scholar 

  8. Wang Y, Wang W, Gong F, Fu S, Zhang Q, Hu J, et al. Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease. Arthritis Rheum. 2013;65:805–14.

    Article  CAS  PubMed  Google Scholar 

  9. Takahara T, Shimizu M, Nakagishi Y, Kinjo N, Yachie A. Serum IL-18 as a potential specific marker for differentiating systemic juvenile idiopathic arthritis from incomplete Kawasaki disease. Rheumatol Int. 2015;35:81–4.

    Article  CAS  PubMed  Google Scholar 

  10. Yamamoto N, Sato K, Hoshina T, Kojiro M, Kusuhara K. Utility of ferritin as a predictor of the patients with Kawasaki disease refractory to intravenous immunoglobulin therapy. Mod Rheumatol. 2015;25:898–902.

    Article  CAS  PubMed  Google Scholar 

  11. Nasir A, Al Tatari H, Hamdan MA. Very high serum ferritin levels in three newborns with Kawasaki-like illness. Paediatr Child Health. 2012;17:201–4.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Noto T, Seto H, Fukuhara J, Murabayashi M, Yachie A, Ayusawa M, et al. A case of incomplete Kawasaki disease with extremely high serum ferritin and interleukin-18 levels. BMC Pediatr. 2018;18:386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mizuta M, Shimizu M, Inoue N, Kasai K, Nakagishi Y, Takahara T, et al. Serum ferritin levels as a useful diagnostic marker for the distinction of systemic juvenile idiopathic arthritis and Kawasaki disease. Mod Rheumatol. 2016;26:929–32.

    Article  CAS  PubMed  Google Scholar 

  14. Soomro AY, Guerchicoff A, Nichols DJ, Suleman J, Dangas GD. The current role and future prospects of D-dimer biomarker. Eur Heart J Cardiovasc Pharmacother. 2016;2:175–84.

    Article  CAS  PubMed  Google Scholar 

  15. Imamura T, Yoshihara T, Yokoi K, Nakai N, Ishida H, Kasubuchi Y. Impact of increased D-dimer concentrations in Kawasaki disease. Eur J Pediatr. 2005;164:526–7.

    Article  CAS  PubMed  Google Scholar 

  16. Masuzawa Y, Mori M, Hara T, Inaba A, Oba MS, Yokota S. Elevated D-dimer level is a risk factor for coronary artery lesions accompanying intravenous immunoglobulin-unresponsive Kawasaki disease. Ther Apher Dial. 2015;19:171–7.

    Article  CAS  PubMed  Google Scholar 

  17. Zhou Y, Wang S, Zhao J, Fang P. Correlations of complication with coronary arterial lesion with VEGF, PLT, D-dimer and inflammatory factor in child patients with Kawasaki disease. Eur Rev Med Pharmacol Sci. 2018;22:5121–6.

    CAS  PubMed  Google Scholar 

  18. Righini M, Perrier A, De Moerloose P, Bounameaux H. D-dimer for venous thromboembolism diagnosis: 20 years later. J Thromb Haemost. 2008;6:1059–71.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported, in part, by grants from The National Natural Science Foundation of China (81670251).

Author information

Author notes

  1. Wei-Xing Kong and Fei-Yue Ma contributed equally to this paper.

Authors and Affiliations

  1. Department of Cardiovascular Diseases, Children’s Hospital, Zhejiang University School of Medicine, 3333 Binsheng Road, Hangzhou 310052, China

    Wei-Xing Kong, Fei-Yue Ma, Song-Ling Fu, Wei Wang, Chun-Hong Xie, Yi-Ying Zhang & Fang-Qi Gong

Authors
  1. Wei-Xing Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fei-Yue Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Song-Ling Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chun-Hong Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yi-Ying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fang-Qi Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KWX and MFY conceptualized and designed the study, acquired, analyzed and interpreted data, drafted the initial manuscript. FSL, WW, XCH and ZYY acquired, analyzed and interpreted data. GFQ conceptualized and designed the study, coordinated and supervised data collection and analysis, critically reviewed the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Fang-Qi Gong.

Ethics declarations

Ethical approval

This study was approved and reviewed by the Ethics Committee of the Children’s Hospital, Zhejiang University School of Medicine.

Conflict of interest

No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kong, WX., Ma, FY., Fu, SL. et al. Biomarkers of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease. World J Pediatr 15, 168–175 (2019). https://doi.org/10.1007/s12519-019-00234-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12519-019-00234-6

Keywords

Search

Navigation